| Atrial natriuretic peptide (ANP) is a member of the cardiac natriuretic peptide family synthesized as pre-proANP in atrial myocytes, processed in secretory granules to proANP, and then cleaved by the transmembrane serine protease corin at the time of secretion to generate the biologically active circulating hormone, which belongs to the same family as brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) and shares the conserved disulfide-bonded ring structure required for receptor binding. The mature peptide contains a central 17-residue ring formed by an intramolecular disulfide bridge flanked by flexible N- and C-terminal segments, and this ring engages guanylyl cyclase–linked natriuretic peptide receptor-A (NPR-A, also termed GC-A) on target cells to activate the intrinsic cyclase domain, increase intracellular cGMP, and initiate downstream signaling. ANP–NPR-A signaling activates cGMP-dependent protein kinase G and cGMP-regulated phosphodiesterases and ion channels, lowers cytosolic calcium in vascular smooth muscle, and produces vasodilation, while in the kidney it acts on glomerular and tubular targets to increase glomerular filtration rate, inhibit sodium reabsorption in the collecting duct, and enhance natriuresis and diuresis, thereby reducing plasma volume and arterial blood pressure. ANP also suppresses the renin–angiotensin–aldosterone system by inhibiting renin and aldosterone secretion and decreases sympathetic nervous system activity, so that the peptide functions as a coordinated counter-regulatory hormone opposing vasoconstrictor and sodium-retaining pathways and stabilizing cardiovascular and volume homeostasis. Secretion of ANP is tightly coupled to atrial wall stretch; mechanical distension of the atria by volume loading or increased venous return triggers rapid exocytosis of ANP-containing granules, and atrial tachyarrhythmias, vasoconstrictor-induced increases in preload or afterload, and endothelial factors such as endothelin and nitric oxide further modulate release, establishing atrial stretch and paracrine signaling as primary determinants of circulating ANP levels. At the transcriptional level, ANP expression is predominantly atrial under physiological conditions but becomes strongly upregulated in stressed ventricles, and the ANP gene is a well-established marker of pathological cardiac hypertrophy and remodeling, where elevated myocardial and plasma ANP reflect increased wall stress and altered hemodynamic load. In renal and cardiovascular disease, circulating ANP levels rise in states of volume expansion such as heart failure and chronic kidney disease and contribute to compensatory natriuretic and vasodilator responses, while impaired ANP signaling or reduced receptor responsiveness associate with hypertension, cardiac hypertrophy, and progression of heart failure. |
